Cross-species comparative DNA methylation reveals novel insights into complex traits genetics among cattle, sheep and goats

The cross-species characterization of evolutionary changes in the functional genome can facilitate the translation of genetic findings across species and the interpretation of the evolutionary basis underlying complex phenotypes. Yet, this has not been fully explored between cattle, sheep, goats, and other mammals. Here, we systematically characterized the evolutionary dynamics of DNA methylation and gene expression in three somatic tissues (i.e., brain, liver, and skeletal muscle) and sperm across seven mammalian species, including three ruminant livestock species (cattle, sheep, and goats), humans, pigs, mice, and dogs, by generating and integrating 160 DNA methylation and transcriptomic datasets. We demonstrate dynamic changes of DNA hypomethylated regions (HypoMRs) and hypermethylated regions (HyperMRs) in tissue-type manner across cattle, sheep, and goats. Specifically, based on the phylo-epigenetic model of DNA methylome, we identified a total of 25,074 HypoMR extension events specific to cattle, which participated in rewiring tissue-specific regulatory network. Furthermore, by integrating genome-wide association studies (GWAS) of 50 cattle traits, we provided novel insights into the genetic and evolutionary basis of complex phenotypes in cattle. Overall, our study provides a valuable resource for exploring the evolutionary dynamics of the functional genome and highlights the importance of cross-species characterization of multi-omics datasets for the evolutionary interpretation of complex phenotypes in cattle livestock.